Bhumasamudram Jagadish1, Gerald P. Guntle2,
Vijay Gokhale3, Amanda F. Baker2, Eugene A. Mash1,
Natarajan Raghunand4
1Chemistry, The University of Arizona,
Tucson, AZ, United States; 2Cancer Center, The University of
Arizona, Tucson, AZ, United States; 3Pharmacology &
Toxicology, The University of Arizona, Tucson, AZ, United States; 4Radiology,
The University of Arizona, Tucson, AZ, United States
DO3A-
and DOTA-based thiol complexes of gadolinium have been synthesized and
characterized. The molecules are designed to covalently bind the conserved
cysteine-34 site in circulating plasma albumin. Redox-sensitivity is
conferred by differential relaxivities of the albumin-bound (in oxidizing
microenvironments) and unbound (in reducing microenvironments) forms of the
complexes. Oxidative stress was induced in tumor-bearing mice by
2-deoxyglucose challenge. The change in tumor T1 following administration of
a candidate thiol complex of Gd was significantly lower in treated mice
relative to control mice. This is consistent with a 2DG-induced ARE-driven
reduction of the tumor microenvironment, and supporting evidence will be
presented.